A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus
Extract: Development of the constrictor response of the ductus arteriosus to O2 and selected vasoactive drugs (acetylcholine and bradykinin) was studied in 20 fetal lambs weighing 680–4800 g (90− to 150-day gestation). The isolated ductus arteriosus was perfused in vitro with Tyrode's solution at constant flow, temperature (38°), pH (7.3–7.4), and Pco2 (30–40 mm Hg), and the mean pressure difference across the ductus was measured. Ductal resistance was calculated at different levels of PO2 (10–700 mm Hg), raised stepwise to produce dose-response curves. Three young fetuses failed to respond initially to O2 and in the other 17 the initial response occurred at progressively lower PO2 levels with advancing gestation. The maximal degree of constriction developed showed a progressive increase with advancing gestational age.At any given PO2, both acetylcholine and bradykinin produced a further increase in resistance when added to the perfusion solution, but this further increase was independent of age. The level of PO2 at which an initial response occurred was decreased after exposure to acetylcholine but not bradykinin.Speculation: The ductus arteriosus of the fetal lamb constricts when exposed to oxygen. The initial level of PO2 at which this constriction occurs decreases, and the maximal degree of constriction increases, with advancing gestational age. The poor response to oxygen of the ductus arteriosus in the immature fetus may be the mechanism responsible for the high incidence of patent ductus arteriosus in premature infants. Constriction following-oxygen may be augmented by the exposure to acetylcholine or bradykinin.